Contribution of autosomal loci and the Y chromosome to the stress response in rats

被引:27
作者
Dumas, P
Pausová, Z
Kren, V
Krenová, D
Pravenec, M
Dumont, M
Ely, D
Turner, M
Sun, YL
Tremblay, J
Hamet, P
机构
[1] Univ Montreal, CHUM, Ctr Rech, Lab Cellular Biol Hypertens, Montreal, PQ H2W 1T8, Canada
[2] Univ Montreal, CHUM, Ctr Rech, Mol Med Lab, Montreal, PQ H2W 1T8, Canada
[3] Charles Univ, Fac Med 1, Inst Biol, Prague, Czech Republic
[4] Acad Sci Czech Republ, Inst Physiol, Prague, Czech Republic
[5] Univ Akron, Dept Biol, Akron, OH 44325 USA
关键词
stress; linkage (genetic); quantitative trait; sex chromosomes;
D O I
10.1161/01.HYP.35.2.568
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Stress is a critical contributor to cardiovascular diseases through its impact on blood pressure variability and cardiac function. Familial clustering of reactivity to stress has been demonstrated in human subjects, and some rodent models of hypertension are hyperresponsive to stress. Therefore, the present study was designed to uncover the genetic determinants of the stress response. We performed a total genome linkage search to identify the loci of the body temperature response to immobilization stress in a set of recombinant inbred strains (RIS) originating from reciprocal crosses of spontaneously hypertensive rats (SHR) with a normotensive Brown Norway Lx strain. Two quantitative trait loci (QTLs) were revealed on chromosomes (Chrs) 10 and 12 (logarithm of odds scores, 2.2 and 1.3, respectively). The effects of these QTLs were enhanced by a high sodium diet (logarithm of odds scores, 4.0 and 3.3 for Chrs 10 and 12, respectively), which is suggestive of a salt-sensitive component for the phenotype, Congenics for Chr 10 confirmed both the QTL and the salt effect in RIS. Negatively associated loci were also identified on Chrs 8 and 11. Interaction between the loci of Chrs 10 and 12 was demonstrated, with the rat strains bearing SHR alleles at both loci having the highest thermal response to stress. Furthermore, the Y Chr of SHR origin enhanced the response to immobilization stress, as demonstrated in 2 independent models, RIS and Y Chr consomics. However, its full effect requires autosomes of the SHR strain. These findings provide the first evidence for the genetic determination of reactivity to stress with interactions between autosomal loci and between the Y and autosomal Chrs that contribute to the explanation of the 46% of variance in the stress response.
引用
收藏
页码:568 / 573
页数:6
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